Updates and challenges on treatment with BRAF/MEK-inhibitors in melanoma

ABSTRACT

Introduction: Breakthroughs in targeted therapy have significantly improved outcomes for many patients with advanced melanoma, including those with BRAFV600 mutant disease. Targeted therapy for BRAFV600-mutant metastatic melanoma includes combinations of BRAF inhibitors and MEK inhibitors, which improve response rates and prolong progression-free survival (PFS) and overall survival (OS) in these patients. However, while durable responses have been observed, many patients develop acquired resistance to these drugs.

Areas covered: Recent clinical trial updates and ongoing studies with targeted therapy for BRAF-V600 mutant melanoma are reviewed.

Expert opinion: Although BRAF targeted therapy remains an effective treatment for BRAF-mutant for melanoma, ongoing trials are exploring combinations with other targeted therapeutics and immunotherapeutics to determine whether tumor responses can be prolonged, and these drugs are increasingly utilized in the neoadjuvant and adjuvant settings.

KEYWORDS:

• Melanoma
• BRAF
• MEK
• combination therapy

Article highlights

• BRAF inhibitors (vemurafenib, dabrafenib, encorafenib) and MEK inhibitors (cobimetinib, trametinib, binimetinib) are targeted therapy agent for treatment of BRAFV600-mutated advanced melanoma. The combination of BRAF and MEK inhibitors have shown significant improvement in response rates, progression-free survival and overall survival as compared to single-agent targeted therapy, and this combination therapy is the standard of care targeted therapy in patients with BRAFV600-mutated advanced melanoma.

• BRAF and MEK inhibitors are also now FDA-approved in earlier stage melanoma in the adjuvant setting and have shown promising results in the neoadjuvant setting as well.

• Trials utilizing BRAF and MEK inhibitors with different dosing regimens, in combinations with the other targeted therapy agents and immunotherapy agents are ongoing.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was supported by SPORE [Grant number 5P50CA168536].